From Beyond The Rainbow Somewhere

Day: 06/11/2013

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Localizing obscure gastrointestinal bleeding can be a clinical challenge, despite the availability of various endoscopic, imaging, and visceral angiographic techniques. We reviewed the management of patients presenting with obscure gastrointestinal bleeding during the period from 2005 to 2011. Four patients had preoperative localization of the bleeding site with superselective mesenteric angiography, which was confirmed by the use of intraoperative methylene blue injection. This novel technique allowed us to identify the abnormal pathology, and, consequently, resection of the implicated segment of small bowel was performed without any postoperative complications. Final histology showed that 2 patients had arteriovenous malformations: one had a benign hemangioma of the small bowel, and the other had chronic ischemic ulceration in the ileum. Superselective mesenteric angiography combined with intraoperative localization with methylene blue is an important and innovative technique in the management of patients with unclear sources of gastrointestinal bleeding and allows for effective hemorrhage control with a focused and therefore limited bowel resection.

Recent advances in parallel genomic processing and computational mapping have been applied to the native human microbial environment to provide a new understanding of the role of the microbiome in health and disease. In particular, studies of the distal gut microbiome have proposed that changes in gut microbiota are related to obesity, the metabolic syndrome, and Western diet. We examined the changes in the distal gut microbiome composition as it relates to the lean and obese phenotypes, particularly after surgical weight loss. A PubMed search of publications from January 1, 2005, through December 31, 2012, used the search terms weight, obesity, microbiome, andbariatric surgery. We included studies that provided information on subjects’ weight and/or body mass index and a formal assessment of the microbiome. Certain bacteria, specifically the archaeonMethanobrevibacter smithii, have enhanced ability to metabolize dietary substrate, thereby increasing host energy intake and weight gain. With weight loss, there is a decrease in the ratio of Firmicutes to Bacteroidetes phyla. One major finding from microbial sequencing analyses after Roux-en-Y gastric bypass is the comparative overabundance of Proteobacteria in the distal gut microbiome, which is distinct from the changes seen in weight loss without Roux-en-Y gastric bypass. This review provides the practicing surgeon with (1) an update on the state of a rapidly innovating branch of clinical bioinformatics, specifically, the microbiome; (2) a new understanding of the microbiome changes after Roux-en-Y gastric bypass and weight loss; and (3) a basis for understanding further clinical applications of studies of the distal gut microbiome, such as in Crohn disease, ulcerative colitis, and infectious colitis.

Design We conducted a detailed immunohistochemical analysis of pathological NDAPs other than PrPsc in human pituitary glands. We also searched for ND in recipients of pituitary-derived c-hGH by reviewing the National Hormone and Pituitary Program (NHPP) cohort database and medical literature.

Setting University-based academic center and agencies of the US Department of Health and Human Services.

Participants Thirty-four routine autopsy subjects (10 non-ND controls and 24 patients with ND) and a US cohort of c-hGH recipients in the NHPP.

Main Outcome Measures Detectable NDAPs in human pituitary sections and death certificate reports of non-PrPsc ND in the NHPP database.

Results We found mild amounts of pathological tau, Aβ, and α-synuclein deposits in the adeno/neurohypophysis of patients with ND and control patients. No cases of AD or PD were identified, and 3 deaths attributed to amyotrophic lateral sclerosis (ALS) were found among US NHPP c-hGH recipients, including 2 of the 796 decedents in the originally confirmed NHPP c-hGH cohort database.

Conclusions and Relevance Despite the likely frequent exposure of c-hGH recipients to NDAPs, and their markedly elevated risk of PrPsc-related disease, this population of NHPP c-hGH recipients does not appear to be at increased risk of AD or PD. We discovered 3 ALS cases of unclear significance among US c-hGH recipients despite the absence of pathological deposits of ALS-associated proteins (TDP-43, FUS, and ubiquilin) in human pituitary glands. In this unique in vivo model of human-to-human transmission, we found no evidence to support concerns that NDAPs underlying AD and PD transmit disease in humans despite evidence of their cell-to-cell transmission in model systems of these disorders. Further monitoring is required to confirm these conclusions.

Chronic neuropathic pain, caused by lesions in the peripheral or central nervous system, comes in many forms. We describe current approaches to the diagnosis and assessment of neuropathic pain and discuss the results of recent research on its pathophysiologic mechanisms. Randomized controlled clinical trials of gabapentin, the 5% lidocaine patch, opioid analgesics, tramadol hydrochloride, and tricyclic antidepressants provide an evidence-based approach to the treatment of neuropathic pain, and specific recommendations are presented for use of these medications. Continued progress in basic and clinical research on the pathophysiologic mechanisms of neuropathic pain may make it possible to predict effective treatments for individual patients by application of a pain mechanism–based approach.

Chronic neuropathic pain is common in clinical practice. Patients with conditions as diverse as diabetic polyneuropathy, human immunodeficiency virus (HIV) sensory neuropathy, poststroke syndromes, and multiple sclerosis frequently experience daily pain that greatly impairs their quality of life. Table 1 divides common chronic neuropathic pain syndromes into 2 groups based on a central or peripheral location of the nervous system lesion. It is probable, however, that both peripheral and central nervous system mechanisms contribute to the persistence of most types of neuropathic pain. Although precise estimates of the prevalence of neuropathic pain are not available, it is more common than has generally been appreciated. In the United States, there may be more than 3 million people with painful diabetic neuropathy (PDN)1 and as many as 1 million with postherpetic neuralgia (PHN)

Interest in the mechanisms and treatment of chronic neuropathic pain has increased during the past several years, and this is likely to result in significant treatment advances in the future. These advances will make it possible to go beyond the determination of whether treatment is effective to the identification of what treatments are most effective for which patients.13,67 Progress in basic science will lead to a greater understanding of the pathophysiologic mechanisms of neuropathic pain. Important goals for clinical research are to devise methods for reliably identifying specific mechanisms in individual patients and to target treatment to them.13– 17 Greater attention should also be paid to developing preventive interventions for patients who are at risk for chronic neuropathic pain, including patients undergoing breast cancer surgery,68 those with herpes zoster,69 and those with diabetes.

Importance Individuals with the fragile X premutation express expanded CGG repeats (repeats 55-200) in the FMR1 gene and elevated FMR1 messenger RNA (mRNA) levels, both of which may underlie the occurrence of the late-onset neurodegenerative disorder fragile X–associated tremor/ataxia syndrome (FXTAS). Because the core feature of FXTAS is motor impairment, determining the influence of FMR1 mRNA levels on structural connectivity of motor fiber tracts is critical for a better understanding of the pathologic features of FXTAS.

Objective To examine the associations of CGG repeat and FMR1 mRNA with motor-related fiber tracts in males with premutation alleles.

Design and Setting A case-control study conducted at the University of California, Davis, from April 1, 2008, through August 31, 2009. All data were collected masked to the carrier status of theFMR1 gene.

Participants Thirty-six male premutation carriers with FXTAS and 26 male premutation carriers without FXTAS were recruited through their family relationships with children affected by fragile X syndrome. The controls were 34 unaffected family members and healthy volunteers from the local community.

Main Outcomes and Measures The CGG repeat lengths and FMR1 mRNA expression levels in peripheral blood lymphocytes, motor functioning, and white matter structural integrity that were estimated using diffusion tensor imaging. After data collection, we selected 4 motor tracts to reconstruct using diffusion tensor tractography, namely, the middle and superior cerebellar peduncles, descending motor tracts (containing the corticospinal, corticobulbar, and corticopontine tracts), and the anterior body of the corpus callosum.

Conclusions and Relevance Distinct pathophysiologic processes may underlie the structural impairment of the motor tracts in FXTAS. Although both the corpus callosum and superior cerebellar peduncles were of great importance to motor functioning, only the superior cerebellar peduncles exhibited an association with the elevated RNA levels in the blood of fragile X premutation carriers.

Localizing obscure gastrointestinal bleeding can be a clinical challenge, despite the availability of various endoscopic, imaging, and visceral angiographic techniques. We reviewed the management of patients presenting with obscure gastrointestinal bleeding during the period from 2005 to 2011. Four patients had preoperative localization of the bleeding site with superselective mesenteric angiography, which was confirmed by the use of intraoperative methylene blue injection. This novel technique allowed us to identify the abnormal pathology, and, consequently, resection of the implicated segment of small bowel was performed without any postoperative complications. Final histology showed that 2 patients had arteriovenous malformations: one had a benign hemangioma of the small bowel, and the other had chronic ischemic ulceration in the ileum. Superselective mesenteric angiography combined with intraoperative localization with methylene blue is an important and innovative technique in the management of patients with unclear sources of gastrointestinal bleeding and allows for effective hemorrhage control with a focused and therefore limited bowel resection.

Importance Calcium intake has been promoted because of its proposed benefit on bone health, particularly among the older population. However, concerns have been raised about the potential adverse effect of high calcium intake on cardiovascular health.

Objective To investigate whether intake of dietary and supplemental calcium is associated with mortality from total cardiovascular disease (CVD), heart disease, and cerebrovascular diseases.

Design and Setting Prospective study from 1995 through 1996 in California, Florida, Louisiana, New Jersey, North Carolina, and Pennsylvania and the 2 metropolitan areas of Atlanta, Georgia, and Detroit, Michigan.

Participants A total of 388 229 men and women aged 50 to 71 years from the National Institutes of Health–AARP Diet and Health Study.

Main Outcome Measures Dietary and supplemental calcium intake was assessed at baseline (1995-1996). Supplemental calcium intake included calcium from multivitamins and individual calcium supplements. Cardiovascular disease deaths were ascertained using the National Death Index. Multivariate Cox proportional hazards regression models adjusted for demographic, lifestyle, and dietary variables were used to estimate relative risks (RRs) and 95% CIs.

Results During a mean of 12 years of follow-up, 7904 and 3874 CVD deaths in men and women, respectively, were identified. Supplements containing calcium were used by 51% of men and 70% of women. In men, supplemental calcium intake was associated with an elevated risk of CVD death (RR>1000 vs 0 mg/d, 1.20; 95% CI, 1.05-1.36), more specifically with heart disease death (RR, 1.19; 95% CI, 1.03-1.37) but not significantly with cerebrovascular disease death (RR, 1.14; 95% CI, 0.81-1.61). In women, supplemental calcium intake was not associated with CVD death (RR, 1.06; 95% CI, 0.96-1.18), heart disease death (1.05; 0.93-1.18), or cerebrovascular disease death (1.08; 0.87-1.33). Dietary calcium intake was unrelated to CVD death in either men or women.

Conclusions and Relevance Our findings suggest that high intake of supplemental calcium is associated with an excess risk of CVD death in men but not in women. Additional studies are needed to investigate the effect of supplemental calcium use beyond bone health.

Importance The benefits of fluid and sodium restriction in patients hospitalized with acute decompensated heart failure (ADHF) are unclear.

Objective To compare the effects of a fluid-restricted (maximum fluid intake, 800 mL/d) and sodium-restricted (maximum dietary intake, 800 mg/d) diet (intervention group [IG]) vs a diet with no such restrictions (control group [CG]) on weight loss and clinical stability during a 3-day period in patients hospitalized with ADHF.

InterventionFluid restriction (maximum fluid intake, 800 mL/d) and additional sodium restriction (maximum dietary intake, 800 mg/d) were carried out until the seventh hospital day or, in patients whose length of stay was less than 7 days, until discharge. The CG received a standard hospital diet, with liberal fluid and sodium intake.

Main Outcomes and MeasuresWeight loss and clinical stability at 3-day assessment, daily perception of thirst, and readmissions within 30 days.

Results Seventy-five patients were enrolled (IG, 38; CG, 37). Most were male; ischemic heart disease was the predominant cause of heart failure (17 patients [23%]), and the mean (SD) left ventricular ejection fraction was 26% (8.7%). The groups were homogeneous in terms of baseline characteristics. Weight loss was similar in both groups (between-group difference in variation of 0.25 kg [95% CI, −1.95 to 2.45]; P = .82) as well as change in clinical congestion score (between-group difference in variation of 0.59 points [95% CI, −2.21 to 1.03]; P = .47) at 3 days. Thirst was significantly worse in the IG (5.1 [2.9]) than the CG (3.44 [2.0]) at the end of the study period (between-group difference, 1.66 points; time × group interaction; P = .01). There were no significant between-group differences in the readmission rate at 30 days (IG, 11 patients [29%]; CG, 7 patients [19%]; P = .41).

Conclusions and Relevance Aggressive fluid and sodium restriction has no effect on weight loss or clinical stability at 3 days and is associated with a significant increase in perceived thirst. We conclude that sodium and water restriction in patients admitted for ADHF are unnecessary.

Importance Patients undergoing hemodialysis have an annual mortality rate exceeding 20%, comparable to many types of cancer. Past research has shown that patients with cancer overestimate their likelihood of survival relative to their physicians, but this relationship has not been examined in patients with noncancer diagnoses. Perceptions of prognosis and transplant candidacy may influence goals of care.

Objectives To compare the perceptions of hemodialysis patients and their nephrologists concerning prognosis and the likelihood of transplant; to follow actual survival; and to explore the relationship between patients’ expectations and their goals of care.

Design We completed a medical record abstraction to estimate 1-year mortality risk among patients who underwent dialysis at any time from November 1, 2010, through September 1, 2011. We then conducted in-person interviews with eligible patients whose predicted 1-year mortality, based on validated prognostic tools, was at least 20%. We also interviewed their nephrologists. We compared patients’ and physicians’ expectations about 1- and 5-year survival and transplant candidacy and measured the association between patients’ expectations and goals of care. We then followed actual survival using Kaplan-Meier methods.

Setting Two dialysis units in Boston.

Participants Two hundred seven patients undergoing hemodialysis included in the medical record review, with 62 eligible patients interviewed.

Main Outcomes and Measures Predicted 1-year mortality risk using validated prognostic tools; actual survival; patients’ and physicians’ expectations about 1-year survival and likelihood of transplant; and patients’ goals of care.

Results Of the 207 hemodialysis patients, 72.5% had a predicted 1-year mortality of at least 20%. Of the 80 patients eligible for interview, 62 participated (response rate, 78%). Patients were significantly more optimistic than their nephrologists about 1- and 5-year survival (P < .001 for both) and were more likely to think they were transplant candidates (37 [66%] vs 22 [39%] [P = .008]). Of the 81% of patients reporting a 90% chance or greater of being alive at 1 year, 18 (44%) preferred care focused on extending life, even if it meant more discomfort, compared with 1 (9%) among patients reporting a lower chance of survival (P = .045). Actual survival was 93% at 1 year but decreased to 79% by 17 months and 56% by 23 months.

Conclusions and Relevance Hemodialysis patients are more optimistic about prognosis and transplant candidacy than their nephrologists. In our sample, patients’ expectations about 1-year survival were more accurate than those of their nephrologists, but their longer-term survival expectations dramatically overestimated even their 2-year survival rates. Patients’ prognostic expectations are associated with their treatment preferences. Our findings suggest the need for interventions to help providers communicate effectively with patients about prognosis.

ParticipantsTricare Prime/Plus beneficiaries evaluated from October 1, 2003, to March 1, 2010.

Interventions Statin use during fiscal year 2005. On the basis of medication fills, patients were divided into 2 groups: statin users (received a statin for at least 90 days) and nonusers (never received a statin throughout the study period).

Main Outcomes and Measures Using patients’ baseline characteristics, we generated a propensity score that was used to match statin users and nonusers; odds ratios (ORs) were determined for each outcome measure. Secondary analyses determined adjusted ORs for all patients who met study criteria and a subgroup of patients with no comorbidities identified using the Charlson Comorbidity Index. Sensitivity analysis further determined adjusted ORs for a subgroup of patients with no musculoskeletal diseases at baseline and a subgroup of patients who continued statin therapy for 2 years or more. The occurrence of musculoskeletal conditions was determined using prespecified groups of International Classification of Diseases, Ninth Revision, ClinicalModification codes: Msk1, all musculoskeletal diseases; Msk1a, arthropathies and related diseases; Msk1b, injury-related diseases (dislocation, sprain, strain); and Msk2, drug-associated musculoskeletal pain.

Conclusions and Relevance Musculoskeletal conditions, arthropathies, injuries, and pain are more common among statin users than among similar nonusers. The full spectrum of statins’ musculoskeletal adverse events may not be fully explored, and further studies are warranted, especially in physically active individuals.